The long-term objective of this proposal is to characterize fundamental properties of chemosensory function, using gustatory neurons in the pharynx of Drosophila melanogaster as a model for investigating taste-based behaviors. Small numbers of gustatory neurons can have large effects on feeding in model organisms like Drosophila, where evolutionarily conserved mechanisms of taste perception can be studied using a robust neuro-genetic toolkit. The first aim is to test if the Drosophila pharynx mediates either the acceptance or rejection of food into the digestive tract. These experiments will address a major issue: despite their possible role in dietary regulation, remarkably little is known about how pharyngeal neurons influence feeding. Pharyngeal neurons in transgenic flies will be specifically tested~ I will inducibly silence or activate only pharyngeal neurons during a series of feedin assays. A likely outcome of this aim is that the manipulation of certain pharyngeal sensory neurons will cause changes in feeding responses, thereby substantiating the relatively uncharacterized Drosophila pharynx as a feeding checkpoint that mediates acceptance or rejection of different foods. The second aim is to test whether a novel family of ionotropic glutamate receptors (IRs) is functionally required for sensory detection in pharyngeal neurons. IR genes appear to be expressed in pharyngeal sensory neurons, but their role in gustatory sensing has not yet been tested. To address this issue, I will assay the feeding responses of both mutants and targeted RNAi knockdown flies that possess a loss-of-function in different IR genes. The demonstration that IRs are required for gustatory responses would have significant implications for taste perception, since IRs have thus far only been implicated in olfactory sensing. Defects in gustatory detection diminish an organism's ability to avoid dangers in the environment, and changes to chemosensory perception may have drastic effects on dietary regulation, as recent studies suggest altering taste sensitivities can lead to increased rates of obesity in humans. Thus, uncovering basic principles of taste perception could lead to new methods of controlling insect vectors of disease and managing human dietary regulation.